Wastewater surveillance for SARS-CoV-2 to support return to campus: Methodological considerations and data interpretation.

The COVID-19 pandemic has been challenging for various institutions such as school systems due to widespread closures. As schools re-open their campuses to in-person education, there is a need for frequent screening and monitoring of the virus to ensure the safety of students and staff and to limit risk to the surrounding community. Wastewater surveillance (WWS) of SARS-CoV-2 is a rapid and economical approach to determine the extent of COVID-19 in the community. The focus of this review is on the emergence of WWS as a tool for safe return to school campuses, taking into account methodological considerations such as site selection, sample collection and processing, SARS-CoV-2 quantification, and data interpretation. Recently published studies on the implementation of COVID-19 WWS on school and college campuses were reviewed. While there are several logistical and technical challenges, WWS can be used to inform decision-making at the school campus and/or building level.

Results from the WHO external quality assessment for the respiratory syncytial virus pilot, 2016-17.

BACKGROUND: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. METHODS: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. RESULTS: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. CONCLUSIONS: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended.

Genetic evolution of influenza viruses among selected countries in Latin America, 2017-2018.

OBJECTIVE: Since the 2009 influenza pandemic, Latin American (LA) countries have strengthened their influenza surveillance systems. We analyzed influenza genetic sequence data from the 2017 through 2018 Southern Hemisphere (SH) influenza season from selected LA countries, to map the availability of influenza genetic sequence data from, and to describe, the 2017 through 2018 SH influenza seasons in LA. METHODS: We analyzed influenza A/H1pdm09, A/H3, B/Victoria and B/Yamagata hemagglutinin sequences from clinical samples from 12 National Influenza Centers (NICs) in ten countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, Paraguay, Peru and Uruguay) with a collection date from epidemiologic week (EW) 18, 2017 through EW 43, 2018. These sequences were generated by the NIC or the WHO Collaborating Center (CC) at the U.S Centers for Disease Control and Prevention, uploaded to the Global Initiative on Sharing All Influenza Data (GISAID) platform, and used for phylogenetic reconstruction. FINDINGS: Influenza hemagglutinin sequences from the participating countries (A/H1pdm09 n = 326, A/H3 n = 636, B n = 433) were highly concordant with the genetic groups of the influenza vaccine-recommended viruses for influenza A/H1pdm09 and influenza B. For influenza A/H3, the concordance was variable. CONCLUSIONS: Considering the constant evolution of influenza viruses, high-quality surveillance data-specifically genetic sequence data, are important to allow public health decision makers to make informed decisions about prevention and control strategies, such as influenza vaccine composition. Countries that conduct influenza genetic sequencing for surveillance in LA should continue to work with the WHO CCs to produce high-quality genetic sequence data and upload those sequences to open-access databases.

Leveraging the Global Influenza Surveillance and Response System for global respiratory syncytial virus surveillance-opportunities and challenges.

BACKGROUND: Respiratory syncytial virus (RSV)-associated acute lower respiratory infection is a common cause for hospitalization and hospital deaths in young children globally. There is urgent need to generate evidence to inform immunization policies when RSV vaccines become available. The WHO piloted a RSV surveillance strategy that leverages the existing capacities of the Global Influenza Surveillance and Response System (GISRS) to better understand RSV seasonality, high-risk groups, validate case definitions, and develop laboratory and surveillance standards for RSV. METHODS: The RSV sentinel surveillance strategy was piloted in 14 countries. Patients across all age groups presenting to sentinel hospitals and clinics were screened all year-round using extended severe acute respiratory infection (SARI) and acute respiratory infection (ARI) case definitions for hospital and primary care settings, respectively. Respiratory specimens were tested for RSV at the National Influenza Centre (NIC) using standardized molecular diagnostics that had been validated by an External Quality Assurance program. The WHO FluMart data platform was adapted to receive case-based RSV data and visualize interactive visualization outputs. RESULTS: Laboratory standards for detecting RSV by RT-PCR were developed. A review assessed the feasibility and the low incremental costs for RSV surveillance. Several challenges were addressed related to case definitions, sampling strategies, the need to focus surveillance on young children, and the data required for burden estimation. CONCLUSIONS: There was no evidence of any significant adverse impact on the functioning of GISRS which is primarily intended for virologic and epidemiological surveillance of influenza.

Clinical characteristics, predictors, and performance of case definition-Interim results from the WHO global respiratory syncytial virus surveillance pilot.

BACKGROUND: The lack of a uniform surveillance case definition poses a challenge to characterize the epidemiology, clinical features, and disease burden of the respiratory syncytial virus (RSV). Global standards for RSV surveillance will inform immunization policy when RSV vaccines become available. METHODS: The WHO RSV surveillance pilot leverages the capacities of the Global Influenza Surveillance and Response System (GISRS). Hospitalized and non-hospitalized medically attended patients of any age were tested for RSV using standardized molecular diagnostics throughout the year in fourteen countries. An extended severe acute respiratory infection (extended SARI) or an acute respiratory infection (ARI) case definition was used that did not require fever as a criterion. RESULTS: Amongst 21 221 patients tested for RSV between January 2017 and September 2018, 15 428 (73%) were hospital admissions. Amongst hospitalized RSV-positive patients, 50% were aged <6 months and 88% <2 years. The percentage of patients testing positive for RSV was 37% in children <6 months and 25% in those aged 6 months to 2 years. Patients with fever were less likely to be RSV positive compared to those without fever (OR 0.74; 95% CI: 0.63-0.86). For infants <6 months, 29% of RSV ARI cases did not have fever. CONCLUSION: Requiring fever in a case definition for RSV lowers the sensitivity to detect cases in young children. Countries should consider ways to leverage the GISRS platform to implement RSV surveillance with an augmented case definition amongst the young pediatric population.

Influenza vaccine effectiveness against hospitalizations in children and older adults-Data from South America, 2013-2017. A test negative design.

BACKGROUND: In 2013, the Pan American Health Organization established a multi-site, multi-country network to evaluate influenza vaccine effectiveness (VE). We pooled data from five consecutive seasons in five countries to conduct an analysis of southern hemisphere VE against laboratory-confirmed influenza hospitalizations in young children and older adults. METHODS: We used a test-negative design to estimate VE against laboratory-confirmed influenza in hospitalized young children (aged 6─24 months) and older adults (aged ≥60 years) in Argentina, Brazil, Chile, Colombia, and Paraguay. Following country-specific influenza surveillance protocol, hospitalized persons with severe acute respiratory infections (SARI) at 48 sentinel hospitals (March 2013-December 2017) were tested for influenza virus infection by rRT-PCR. VE was estimated for young children and older adults using logistic random effects models accounting for cluster (country), adjusting for sex, age (months for children, and age-in-year categories for adults), calendar year, country, preexisting conditions, month of illness onset and prior vaccination as an effect modifier for the analysis in adults. RESULTS: We included 8426 SARI cases (2389 children and 6037 adults) in the VE analyses. Among young children, VE against SARI hospitalization associated with any influenza virus was 43% (95%CI: 33%, 51%) for children who received two doses, but was 20% (95%CI: -16%, 45%) and not statistically significant for those who received one dose in a given season. Among older adults, overall VE against SARI hospitalization associated with any influenza virus was 41% (95%CI: 28%, 52%), 45% (95%CI: 34%, 53%) against A(H3N2), 40% (95%CI: 18%, 56%) against A(H1N1)pdm09, and 20% (95%CI: -40%, 54%) against influenza B viruses. CONCLUSIONS: Our results suggest that over the five-year study period, influenza vaccination programs in five South American countries prevented more than one-third of laboratory confirmed influenza-associated hospitalizations in young children receiving the recommended two doses and vaccinated older adults.

Hospitalizaciones y mortalidad asociada a influenza, Honduras. 2011-2015 / Hospitalizations and deaths associated with Influenza, Honduras. 2011-2015

La carga de enfermedad por influenza está bien documentada en países de clima templado, pero hasta la fecha en Honduras solo se ha realizado un estudio, siendo este el segundo con respecto a la carga médica asociada a influenza. Objetivo: Estimar el número de hospitalizaciones y defunciones, debidos a la influenza, como causante de las infecciones respiratorias agudas en la población. Material yMétodos: Se realizó un estudio descriptivo retrospectivo. Seutilizó tres fuentes de datos secundarias:registros de todos los egresos hospitalarios, resultados de detección viral por influenza y proyecciones de población por grupos de edad. Se estimó la tasa de incidencia y su intervalo de confianza al 95%, combinando las tres fuentes de datos. Resultados: Las hospitalizaciones en las infecciones respiratorias agudas graves (IRAG) J09-J18 asociadas a influenza en el 2011-2015 son mayores en los menores de cinco años, en donde las hospitalizaciones son mayores en los años 2013 con 68.2 (IC 95%: 64.2-72.1) casos por 100, 000 habitantes. En el periodo 2011-2015. Las tasas de incidencia en las defunciones de IRAG asociadas a influenza1.Doctor(a) en medicina y cirugía.2.Doctor(a) en Pediatría3.Nivel Básico de Epidemiologia de Campo del FETP4.MSc.Epidemiólogo del FETP, coordinador de las enfermedades Transmisibles de la unidad devigilancia de la salud, Secretaria de Salud de HondurasAutor de correspondencia: Hommer Mejía, homams2003@yahool.comRecibido: Aprobado: (J09-J18) fueron mayores en el año 2014 con 1 caso (IC 95%: 0.4-1.6) por 100 000 habitantes. La circulación por influenza comenzó a incrementarse a partir de agosto del 2011 luego en los años 2012-2015 con picos altos durante los meses de octubre y noviembre. Conclusión: La carga médica asociada a influenza representa un impacto para los servicios de salud de Honduras, siendo los grupos de población en edades extremas, los que más hospitalizaciones y muertes presentaron. Se sugiere promover la vacunación contra influenza con la composición de cepas circulantes en el país y en temporada apropiada, enfatizando en los grupos más vulnerables de la población...(AU)

The epidemiological signature of influenza B virus and its B/Victoria and B/Yamagata lineages in the 21st century.

We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza.

Burden of influenza-associated respiratory hospitalizations in the Americas, 2010-2015.

BACKGROUND: Despite having influenza vaccination policies and programs, countries in the Americas underutilize seasonal influenza vaccine, in part because of insufficient evidence about severe influenza burden. We aimed to estimate the annual burden of influenza-associated respiratory hospitalizations in the Americas. METHODS: Thirty-five countries in the Americas with national influenza surveillance were invited to provide monthly laboratory data and hospital discharges for respiratory illness (International Classification of Diseases 10th edition J codes 0-99) during 2010-2015. In three age-strata (<5, 5-64, and ≥65 years), we estimated the influenza-associated hospitalizations rate by multiplying the monthly number of respiratory hospitalizations by the monthly proportion of influenza-positive samples and dividing by the census population. We used random effects meta-analyses to pool age-group specific rates and extrapolated to countries that did not contribute data, using pooled rates stratified by age group and country characteristics found to be associated with rates. RESULTS: Sixteen of 35 countries (46%) contributed primary data to the analyses, representing 79% of the America's population. The average pooled rate of influenza-associated respiratory hospitalization was 90/100,000 population (95% confidence interval 61-132) among children aged <5 years, 21/100,000 population (13-32) among persons aged 5-64 years, and 141/100,000 population (95-211) among persons aged ≥65 years. We estimated the average annual number of influenza-associated respiratory hospitalizations in the Americas to be 772,000 (95% credible interval 716,000-829,000). CONCLUSIONS: Influenza-associated respiratory hospitalizations impose a heavy burden on health systems in the Americas. Countries in the Americas should use this information to justify investments in seasonal influenza vaccination-especially among young children and the elderly.

Patterns of influenza B circulation in Latin America and the Caribbean, 2010-2017.

OBJECTIVE: There are limited published data about the circulation of influenza B/Victoria and B/Yamagata in Latin America and the Caribbean (LAC) and most countries have a vaccine policy that includes the use of the trivalent influenza vaccine. We analyzed influenza surveillance data to inform decision-making in LAC about prevention strategies, such as the use of the quadrivalent influenza vaccine. METHODS: There are a total of 28 reference laboratories and National Influenza Centers in LAC that conduct influenza virologic surveillance according to global standards, and on a weekly basis upload their surveillance data to the open-access World Health Organization (WHO) platform FluNet. These data include the number of specimens tested for influenza and the number of specimens positive for influenza by type, subtype and lineage, all by the epidemiologic week of specimen collection. We invited these laboratories to provide additional epidemiologic data about the hospitalized influenza B cases. We conducted descriptive analyses of patterns of influenza circulation and characteristics of hospitalized cases. We compared the predominant B lineage each season to the lineage in the vaccine applied, to determine vaccine mismatch. A Chi-square and Wilcoxan statistic were used to assess the statistical significance of differences in proportions and medians at the P<0.05 level. FINDINGS: During 2010-2017, the annual number of influenza B cases in LAC was ~4500 to 7000 cases. Since 2011, among the LAC-laboratories reporting influenza B lineage using molecular methods, both B/Victoria and B/Yamagata were detected annually. Among the hospitalized influenza B cases, there were statistically significant differences observed between B/Victoria and B/Yamagata cases when comparing age and the proportion with underlying co-morbid conditions and with history of oseltamivir treatment (P<0.001). The proportion deceased among B/Victoria and B/Yamagata hospitalized cases did not differ significantly. When comparing the predominant influenza B lineage detected, as part of surveillance activities during 63 seasons among 19 countries, to the lineage of the influenza B virus included in the trivalent influenza vaccine used during that season, there was a vaccine mismatch noted during 32% of the seasons analyzed. CONCLUSIONS: Influenza B is important in LAC with both B/Victoria and B/Yamagata circulating annually in all sub regions. During approximately one-third of the seasons, an influenza B vaccine mismatch was identified. Further analyses are needed to better characterize the medical and economic burden of each influenza B lineage, to examine the potential cross-protection of one vaccine lineage against the other circulating virus lineage, and to determine the potential impact and cost-effectiveness of using the quadrivalent vaccine rather than the trivalent influenza vaccine.

Estimation of influenza and respiratory syncytial virus hospitalizations using sentinel surveillance data-La Paz, Bolivia. 2012-2017.

OBJECTIVE: The objective was to estimate the number of hospitalizations associated with influenza and RSV using data from severe acute respiratory infection (SARI) sentinel surveillance from El Alto-La Paz. Bolivia. METHODS: All persons who met the case definition for SARI at one sentinel hospital had a clinical sample collected and analyzed by rRT-PCR for influenza and by indirect immunofluorescence for RSV. The SARI-influenza and SARI-RSV case counts were stratified by six age groups. The proportion of cases captured in the sentinel hospital in relation to the non-sentinel hospitals of area was multiplied by the age-specific census population, to build the denominators. The annual incidence and a 95% confidence interval (CI) were estimated. RESULTS: During 2012-2017, n = 2606 SARI cases were reported (average incidence 120/100 000 inhabitants [95% CI: 116-124]); the average incidence of influenza-associated SARI hospitalization was 15.3/100 000 (95% CI: 14.1-16.7), and the average incidence of RSV-associated SARI hospitalization was 9/100 000 inhabitants (95% CI: 8.1-10.1). The highest incidence of influenza was among those less than one year of age (average 174.7/100 000 [range: 89.1-299.5]), followed by those one to four years of age (average 51.8/100 000 [range: 19.8-115.4]) and then those 65 years of age and older (average 47.7/100 000 [range: 18.8-117]). For RSV, the highest incidence was highest among those less than one year of age (231/100 000 [range: 119.9-322.9]). CONCLUSION: Influenza and RSV represent major causes of hospitalization in La Paz, Bolivia-with the highest burden among children under one year of age. Our estimates support current prevention strategies in this age group.

Timing of respiratory syncytial virus and influenza epidemic activity in five regions of Argentina, 2007-2016.

BACKGROUND: Within-country differences in the timing of RSV and influenza epidemics have not been assessed in Argentina, the eighth largest country in the world by area. OBJECTIVE: We aimed to compare seasonality for RSV and influenza both nationally and in each of the five regions to inform Argentina's prevention and treatment guidelines. METHOD: The Argentine National Laboratories and Health Institutes Administration collected respiratory specimens from clinical practices, outbreak investigations, and respiratory virus surveillance in 2007-2016; these were tested using immunofluorescence or RT-PCR techniques. We calculated weekly percent positive (PP) and defined season onset as >2 consecutive weeks when PP exceeded the annual mean for the respective year and region. Median season measures (onset, offset and peak) and the established mean method were calculated for each virus. RESULTS: An annual median 59 396 specimens were tested for RSV and 60 931 for influenza; 21-29% tested positive for RSV and 2-7% for influenza. National RSV activity began in April; region-specific start weeks varied by 7 weeks. Duration of RSV activity did not vary widely by region (16-18 weeks in duration). National influenza activity started in June; region-specific start weeks varied by 3 weeks. Duration of influenza epidemic activity varied more by region than that of RSV (7-13 weeks in duration). CONCLUSION: In Argentina, RSV and influenza activity overlapped during the winter months. RSV season tended to begin prior to the influenza season, and showed more variation in start week by region. Influenza seasons tended to vary more in duration than RSV seasons.

Estimating the burden of influenza-associated hospitalizations and deaths in Chile during 2012-2014.

BACKGROUND: Influenza is a vaccine preventable disease that causes important morbidity and mortality worldwide. Estimating the burden of influenza disease is difficult. However, there are some methods based in surveillance data and laboratory testing that can be used for this purpose. OBJECTIVES: Estimating the burden of serious illness from influenza by means of hospitalization and death records during the period between 2012 and 2014, and using information from Severe Acute Respiratory Illness (SARI) surveillance. METHODS: To estimate the Chilean rate of influenza-associated hospitalizations and deaths, we applied the influenza positivity of respiratory samples tested in six SARI surveillance sentinel hospitals to the hospitalizations and deaths from the records with ICD-10 codes from influenza and pneumonia. RESULTS: Annually, 5320 people are hospitalized for influenza and 447 die for this cause. The annual influenza-associated hospitalization rate for the period was 71.5/100 000 person-year for <5 years old, 11.8/100 000 person-year for people between 5 and 64 years old; and 156.0/100 000 person-year for ≥65 years. The annual mortality rate for the period was 0.08/100 000 person-year for <5 years; 0.3/100 000 person-year for people between 5 and 64 years; and 22.8/100 000 person-year for ≥65 years. CONCLUSIONS: This is the first study of influenza burden in Chile. Every year an important quantity of hospitalizations and deaths result from influenza infection. In countries in temperate zones, it is important to know the burden of influenza in order to prepare the health care network and to assess preventive intervention currently in practice and the new ones to implementing.

Revision of clinical case definitions: influenza-like illness and severe acute respiratory infection.

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.

La formulation de définitions précises de cas cliniques fait partie intégrante d'un processus efficace de surveillance de la santé publique. Alors que ces définitions devraient, dans l'idéal, s'appuyer sur un ensemble standardisé et fixe de critères de définition, elles nécessitent souvent une révision pour tenir compte des nouvelles connaissances relatives à la maladie concernée et des améliorations apportées aux tests diagnostiques. Pour être optimales, les définitions de cas doivent aussi établir un équilibre entre sensibilité et spécificité qui reflète leur utilisation aux fins prévues. À la suite de la pandémie de grippe H1N1 de 2009-2010, l'Organisation mondiale de la Santé (OMS) a lancé une consultation technique sur la surveillance mondiale de la grippe. Cela a conduit à des améliorations concernant la sensibilité et la spécificité de la définition de cas pour la grippe ­ c'est-à-dire une maladie respiratoire dont seule la symptomatologie reste à définir. Le processus de révision n'a pas seulement modifié la définition du syndrome de type grippal pour inclure une liste simplifiée des critères le mieux à même de prédire une infection grippale, il a également permis de clarifier le langage utilisé dans la définition pour en améliorer l'interprétation. Par ailleurs, afin de tenir compte des cas sévères de grippe qui nécessitaient une hospitalisation, une nouvelle définition de cas a été introduite concernant l'infection aigüe sévère des voies respiratoires dans tous les groupes d'âge. Il a été constaté que les nouvelles définitions reflétaient davantage de cas, sans pour autant compromettre la spécificité. S'il est vrai que la distinction clinique de la grippe des autres infections respiratoires continue de poser problème, l'utilisation mondiale des nouvelles définitions de cas de l'OMS devrait permettre de dégager des tendances mondiales concernant les caractéristiques et la transmission des virus grippaux ainsi que la charge de morbidité qui leur est associée.

La elaboración de definiciones precisas de los casos clínicos es una parte fundamental de un proceso efectivo de la vigilancia de la salud pública. Aunque tales definiciones deberían, idealmente, estar basadas en una recopilación estandarizada y fija de criterios de definición, a menudo necesitan una revisión para reflejar el nuevo conocimiento de la enfermedad existente y las mejoras en las pruebas de diagnóstico. Las definiciones óptimas de los casos también deben tener un equilibrio entre sensibilidad y especificidad que refleje su uso previsto. Después de la pandemia de gripe H1N1 en 2009-2010, la Organización Mundial de la Salud (OMS) inició una consulta técnica para la vigilancia mundial de la gripe. Esto dio lugar a mejoras en la sensibilidad y la especificidad de las definiciones de los casos de gripe, es decir, una enfermedad respiratoria que carece de una sintomatología definitoria singular. El proceso de revisión no solo modificó la definición de las enfermedades similares a la gripe para incluir una lista simplificada de los criterios que demostraron ser más predictivos de la infección por gripe, sino que también aclaró el lenguaje utilizado para la definición, con el fin de mejorar su interpretación. Para englobar los casos graves de gripe que requirieron hospitalización, también se desarrolló una nueva definición de los casos de la infección respiratoria aguda grave en todos los grupos de edad. Se ha descubierto que las nuevas definiciones engloban más casos sin comprometer la especificidad. A pesar del desafío que todavía plantea la separación clínica de la gripe de otras infecciones respiratorias, el uso global de las nuevas definiciones de los casos de la OMS debería ayudar a determinar las tendencias mundiales en las características y transmisión de los virus de la gripe y la carga de la enfermedad asociada.

Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.

BACKGROUND: Estimates of influenza-associated mortality are important for national and international decision making on public health priorities. Previous estimates of 250 000-500 000 annual influenza deaths are outdated. We updated the estimated number of global annual influenza-associated respiratory deaths using country-specific influenza-associated excess respiratory mortality estimates from 1999-2015. METHODS: We estimated country-specific influenza-associated respiratory excess mortality rates (EMR) for 33 countries using time series log-linear regression models with vital death records and influenza surveillance data. To extrapolate estimates to countries without data, we divided countries into three analytic divisions for three age groups (<65 years, 65-74 years, and ≥75 years) using WHO Global Health Estimate (GHE) respiratory infection mortality rates. We calculated mortality rate ratios (MRR) to account for differences in risk of influenza death across countries by comparing GHE respiratory infection mortality rates from countries without EMR estimates with those with estimates. To calculate death estimates for individual countries within each age-specific analytic division, we multiplied randomly selected mean annual EMRs by the country's MRR and population. Global 95% credible interval (CrI) estimates were obtained from the posterior distribution of the sum of country-specific estimates to represent the range of possible influenza-associated deaths in a season or year. We calculated influenza-associated deaths for children younger than 5 years for 92 countries with high rates of mortality due to respiratory infection using the same methods. FINDINGS: EMR-contributing countries represented 57% of the global population. The estimated mean annual influenza-associated respiratory EMR ranged from 0·1 to 6·4 per 100 000 individuals for people younger than 65 years, 2·9 to 44·0 per 100 000 individuals for people aged between 65 and 74 years, and 17·9 to 223·5 per 100 000 for people older than 75 years. We estimated that 291 243-645 832 seasonal influenza-associated respiratory deaths (4·0-8·8 per 100 000 individuals) occur annually. The highest mortality rates were estimated in sub-Saharan Africa (2·8-16·5 per 100 000 individuals), southeast Asia (3·5-9·2 per 100 000 individuals), and among people aged 75 years or older (51·3-99·4 per 100 000 individuals). For 92 countries, we estimated that among children younger than 5 years, 9243-105 690 influenza-associated respiratory deaths occur annually. INTERPRETATION: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden. The contribution of non-respiratory causes of death to global influenza-associated mortality should be investigated. FUNDING: None.

Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza hospitalizations - Latin America, 2013.

BACKGROUND: Despite widespread utilization of influenza vaccines, effectiveness (VE) has not been routinely measured in Latin America. METHODS: We used a case test-negative control design to estimate trivalent inactivated influenza VE against laboratory-confirmed influenza among hospitalized children aged 6months-5years and adults aged ≥60years which are age-groups targeted for vaccination. We sought persons with severe acute respiratory infections (SARI), hospitalized at 71 sentinel hospitals in Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Honduras, Panama, and Paraguay during January-December 2013. Cases had an influenza virus infection confirmed by real-time reverse transcription PCR (rRT-PCR); controls had a negative rRT-PCR result for influenza viruses. We used a two-stage random effects model to estimate pooled VE per target age-group, adjusting for the month of illness onset, age and preexisting medical conditions. RESULTS: We identified 2620 SARI patients across sites: 246 influenza cases and 720 influenza-negative controls aged ≤5years and 448 cases and 1206 controls aged ≥60years. The most commonly identified subtype among participants (48%) was the influenza A(H1N1)pdm09 virus followed by influenza A(H3N2) (34%) and influenza B (18%) viruses. Among children, the adjusted VE of full vaccination (one dose for previously vaccinated or two if vaccine naïve) against any influenza virus SARI was 47% (95% confidence interval [CI]: 14-71%); VE was 58% (95% CI: 16-79%) against influenza A(H1N1)pdm09, and 65% (95% CI: -9; 89%) against influenza A(H3N2) viruses associated SARI. Crude VE of full vaccination against influenza B viruses associated SARI among children was 3% (95% CI: -150; 63). Among adults aged ≥60years, adjusted VE against any influenza SARI was 48% (95% CI: 34-60%); VE was 54% (95% CI: 37-69%) against influenza A(H1N1)pdm09, 43% (95% CI: 18-61%) against influenza A(H3N2) and 34% (95% CI: -4; 58%) against B viruses associated SARI. CONCLUSION: Influenza vaccine provided moderate protection against severe influenza illness among fully vaccinated young children and older adults, supporting current vaccination strategies.

Estimating the burden of influenza-associated hospitalizations and deaths in Central America.

OBJECTIVES: Our objective was to estimate the incidence of influenza-associated hospitalizations and in-hospital deaths in Central American Region. DESIGN AND SETTING: We used hospital discharge records, influenza surveillance virology data, and population projections collected from Costa Rica, El Salvador, Guatemala, Honduras, and Nicaragua to estimate influenza-associated hospitalizations and in-hospital deaths. We performed a meta-analysis of influenza-associated hospitalizations and in-hospital deaths. MAIN OUTCOME MEASURES: The highest annual incidence was observed among children aged <5 years (136 influenza-associated hospitalizations per 100 000 persons). RESULTS: Annually, 7 625-11 289 influenza-associated hospitalizations and 352-594 deaths occurred in the subregion. CONCLUSIONS: Our results suggest that a substantive number of persons are annually hospitalized because of influenza. Health officials should estimate how many illnesses could be averted through increased influenza vaccination.

Timing of influenza epidemics and vaccines in the American tropics, 2002-2008, 2011-2014.

BACKGROUND: Influenza-associated illness results in increased morbidity and mortality in the Americas. These effects can be mitigated with an appropriately chosen and timed influenza vaccination campaign. To provide guidance in choosing the most suitable vaccine formulation and timing of administration, it is necessary to understand the timing of influenza seasonal epidemics. OBJECTIVES: Our main objective was to determine whether influenza occurs in seasonal patterns in the American tropics and when these patterns occurred. METHODS: Publicly available, monthly seasonal influenza data from the Pan American Health Organization and WHO, from countries in the American tropics, were obtained during 2002-2008 and 2011-2014 (excluding unseasonal pandemic activity during 2009-2010). For each country, we calculated the monthly proportion of samples that tested positive for influenza. We applied the monthly proportion data to a logistic regression model for each country. RESULTS: We analyzed 2002-2008 and 2011-2014 influenza surveillance data from the American tropics and identified 13 (81%) of 16 countries with influenza epidemics that, on average, started during May and lasted 4 months. CONCLUSIONS: The majority of countries in the American tropics have seasonal epidemics that start in May. Officials in these countries should consider the impact of vaccinating persons during April with the Southern Hemisphere formulation.

Associations between seasonal influenza and meteorological parameters in Costa Rica, Honduras and Nicaragua.

Seasonal influenza affects a considerable proportion of the global population each year. We assessed the association between subnational influenza activity and temperature, specific humidity and rainfall in three Central America countries, i.e. Costa Rica, Honduras and Nicaragua. Using virologic data from each country's national influenza centre, rainfall from the Tropical Rainfall Measuring Mission and air temperature and specific humidity data from the Global Land Data Assimilation System, we applied logistic regression methods for each of the five sub-national locations studied. Influenza activity was represented by the weekly proportion of respiratory specimens that tested positive for influenza. The models were adjusted for the potentially confounding co-circulating respiratory viruses, seasonality and previous weeks' influenza activity. We found that influenza activity was proportionally associated (P<0.05) with specific humidity in all locations [odds ratio (OR) 1.21-1.56 per g/kg], while associations with temperature (OR 0.69-0.81 per °C) and rainfall (OR 1.01-1.06 per mm/day) were location-dependent. Among the meteorological parameters, specific humidity had the highest contribution (~3-15%) to the model in all but one location. As model validation, we estimated influenza activity for periods, in which the data was not used in training the models. The correlation coefficients between the estimates and the observed were ≤0.1 in 2 locations and between 0.6-0.86 in three others. In conclusion, our study revealed a proportional association between influenza activity and specific humidity in selected areas from the three Central America countries.